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A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.
Assuntos
Adenocarcinoma , Carcinoma Neuroendócrino , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/genética , Feminino , Masculino , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/genética , Idoso , Adenocarcinoma/patologia , Adenocarcinoma/genética , Adulto , Fatores de Transcrição/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Fusão Gênica , Proteínas do Tecido Nervoso/genética , Proteínas de Fusão Oncogênica/genéticaRESUMO
PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , África Subsaariana , Projetos Piloto , Gradação de TumoresRESUMO
Despite evidence suggesting the importance of psychological resilience for successful aging, little is known about the relationship between diet quality and resilience at different ages. Our study aims to examine the association between diet quality and resilience across the stages of adulthood. Using Stanfords' WELL for Life (WELL) survey data, we conducted a cross-sectional study of diet quality, resilience, sociodemographic, perceived stress, lifestyle, and mental health factors among 6171 Bay Area adults. Diet quality was measured by the WELL Diet Score, which ranges from 0-120. A higher score indicates a better diet quality. Linear regression analysis was used to evaluate the association between the WELL Diet Score and overall resilience and within the following age groups: early young (18-24), late young (25-34), middle (35-49), and late adulthood (≥50). To test whether these associations varied by age groups, an age group by resilience interaction term was also examined. In the fully adjusted model, the WELL Diet Score was positively and significantly associated with overall resilience (all ages (ß = 1.2 ± sd: 0.2, p < 0.001)) and within each age group (early young (ß = 1.1 ± sd: 0.3, p < 0.001); late young (ß = 1.2 ± sd: 0.3, p < 0.001); middle (ß = 0.9 ± sd: 0.3, p < 0.001); and late adulthood (ß = 1.0 ± sd: 0.3, p < 0.001)). Young adults demonstrated the strongest associations between diet quality and resilience. However, there were no significant age-by-resilience interactions. Diet quality may be positively associated with resilience at all stages of adulthood. Further research is needed to determine whether assessing and addressing resilience could inform the development of more effective dietary interventions, particularly in young adults.
Assuntos
Dieta , Resiliência Psicológica , Humanos , Estudos Transversais , Adulto , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Dieta/psicologia , Dieta Saudável/psicologia , Saúde Mental , Estilo de Vida , Fatores Etários , Qualidade de VidaRESUMO
Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10-6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10-8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10-6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.
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Linfoma de Burkitt , Infecções por Vírus Epstein-Barr , Criança , Humanos , Linfoma de Burkitt/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Cadeias alfa de HLA-DQ/genéticaRESUMO
In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10-11 and 3.74×10-2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.
Assuntos
Linfoma de Burkitt , Masculino , Criança , Humanos , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Gana , Aberrações Cromossômicas , Leucócitos/patologia , Imunoglobulinas/genética , Translocação GenéticaRESUMO
Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.
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The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.
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Ácidos Graxos Ômega-3 , Neoplasias da Próstata , Ácidos Graxos trans , Masculino , Humanos , Estados Unidos/epidemiologia , Gana/epidemiologia , Ácidos Graxos Dessaturases/genética , Ácidos Graxos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: We aimed to develop and validate a deep learning system (DLS) by using an auxiliary section that extracts and outputs specific ultrasound diagnostic features to improve the explainable, clinical relevant utility of using DLS for detecting NAFLD. METHODS: In a community-based study of 4144 participants with abdominal ultrasound scan in Hangzhou, China, we sampled 928 (617 [66.5%] females, mean age: 56 years ± 13 [standard deviation]) participants (2 images per participant) to develop and validate DLS, a two-section neural network (2S-NNet). Radiologists' consensus diagnosis classified hepatic steatosis as none steatosis, mild, moderate, and severe. We also explored the NAFLD detection performance of six one-section neural network models and five fatty liver indices on our data set. We further evaluated the influence of participants' characteristics on the correctness of 2S-NNet by logistic regression. RESULTS: Area under the curve (AUROC) of 2S-NNet for hepatic steatosis was 0.90 for ≥ mild, 0.85 for ≥ moderate, and 0.93 for severe steatosis, and was 0.90 for NAFLD presence, 0.84 for moderate to severe NAFLD, and 0.93 for severe NAFLD. The AUROC of NAFLD severity was 0.88 for 2S-NNet, and 0.79-0.86 for one-section models. The AUROC of NAFLD presence was 0.90 for 2S-NNet, and 0.54-0.82 for fatty liver indices. Age, sex, body mass index, diabetes, fibrosis-4 index, android fat ratio, and skeletal muscle via dual-energy X-ray absorptiometry had no significant impact on the correctness of 2S-NNet (p > 0.05). CONCLUSIONS: By using two-section design, 2S-NNet had improved the performance for detecting NAFLD with more explainable, clinical relevant utility than using one-section design. KEY POINTS: ⢠Based on the consensus review derived from radiologists, our DLS (2S-NNet) had an AUROC of 0.88 by using two-section design and yielded better performance for detecting NAFLD than using one-section design with more explainable, clinical relevant utility. ⢠The 2S-NNet outperformed five fatty liver indices with the highest AUROCs (0.84-0.93 vs. 0.54-0.82) for different NAFLD severity screening, indicating screening utility of deep learning-based radiology may perform better than blood biomarker panels in epidemiology. ⢠The correctness of 2S-NNet was not significantly influenced by individual's characteristics, including age, sex, body mass index, diabetes, fibrosis-4 index, android fat ratio, and skeletal muscle via dual-energy X-ray absorptiometry.
Assuntos
Aprendizado Profundo , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População do Leste Asiático , Fibrose , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Ultrassonografia , Adulto , IdosoRESUMO
BACKGROUND: The associations between body flexibility and sarcopenia were not well understood. This study aimed to explore the cross-sectional and longitudinal associations of flexibility with sarcopenia. METHODS: Our study selected participants aged 50-80 from the WELL-China cohort and the Lanxi cohort. Participants from the urban area of the Lanxi cohort were followed up 4 years later. Body flexibility was measured by the sit-and-reach test. Muscle mass was evaluated by dual-energy X-ray absorptiometry. Muscle strength was evaluated using handgrip strength. Sarcopenia was defined as having both low muscle mass and low muscle strength. We used multivariable logistic regressions to assess the cross-sectional associations of body flexibility with low muscle mass, low muscle strength and sarcopenia. We also used multivariable logistic regressions to explore the associations of baseline flexibility and 4-year changes in flexibility with incident low muscle mass, low muscle strength and sarcopenia. RESULTS: A total of 9453 participants were enrolled in the cross-sectional study, and 1233 participants were included in the longitudinal analyses. In the cross-sectional analyses, compared with low body flexibility, high body flexibility was inversely associated with low muscle mass (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.68; P < 0.001), low muscle strength (OR, 0.62; 95% CI, 0.55-0.69; P < 0.001) and sarcopenia (OR, 0.52; 95% CI, 0.41-0.65; P < 0.001), and these associations did not differ in different age groups, sex or physical activity levels. In the longitudinal analyses, compared with participants with low body flexibility, participants with high body flexibility had lower risk of the incident low muscle strength (OR, 0.53; 95% CI, 0.38-0.74; P < 0.001) and sarcopenia (OR, 0.36; 95% CI, 0.21-0.61; P < 0.001), but not incident low muscle mass (OR, 0.59; 95% CI, 0.33-1.06; P = 0.076). Every 1-cm increase in flexibility during 4 years was associated with reduced risk of incident low muscle mass (OR, 0.96; 95% CI, 0.93-1.00; P = 0.025), low muscle strength (OR, 0.96; 95% CI, 0.94-0.98; P = 0.002) and sarcopenia (OR, 0.96; 95% CI, 0.93-0.99; P = 0.007). CONCLUSIONS: High flexibility was associated with reduced risk of incident low muscle strength and sarcopenia. Increases in flexibility were associated with reduced risk of incident low muscle mass, low muscle strength and sarcopenia. Flexibility exercises and monitoring the dynamic change of flexibility might be helpful in preventing sarcopenia among adults aged 50 years or over.
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Sarcopenia , Adulto , Humanos , Sarcopenia/epidemiologia , Estudos Transversais , Força da Mão , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Força Muscular/fisiologiaRESUMO
Positive associations between well-being and a single contemplative practice (e.g., mindfulness meditation) are well documented, yet prior work may have underestimated the strength of the association by omitting consideration of multiple and/or alternative contemplative practices. Moreover, little is known about how contemplative practice behavior (CPB) impacts different dimensions of well-being. This study investigates the relationship of CPB, consisting of four discrete practices (embodied somatic-observing, non-reactive mindfulness, self-compassion, and compassion for others), with multiple dimensions of well-being. As with other canonical lifestyle behaviors, multiple contemplative practices can be integrated into one's daily routine. Thus, it is critical to holistically consider these behaviors, extending them beyond a simple uni-dimensional measure (e.g., daily mindfulness meditation practice). We developed an integrative measure of four types of contemplative practice and found it to be significantly associated with a multi-dimensional measure of well-being. Importantly, our findings were from three large global multi-regional cohorts and compared against better-understood lifestyle behaviors (physical activity). Data were drawn from California/San Francisco Bay Area, (n = 6442), Hangzhou City (n = 10,268), and New Taipei City (n = 3033). In all three cohorts, we found statistically significant (p < 0.05) positive associations between CPB and well-being, both overall and with all of the constituent domains of well-being, comparable to or stronger than the relationship with physical activity across most well-being outcomes. These findings provide robust and cross-cultural evidence for a positive association between CPB and well-being, illuminate dimensions of well-being that could be most influenced by CPB, and suggest CPB may be useful to include as part of fundamental lifestyle recommendations for health and well-being.
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Meditação , Atenção Plena , Humanos , Meditação/métodos , Atenção Plena/métodos , Empatia , São FranciscoRESUMO
BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.
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Estudo de Associação Genômica Ampla , Neoplasias da Próstata , África Subsaariana/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias da Próstata/genética , Fatores de RiscoRESUMO
This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs (noncommunicable diseases). We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown. A total of 3327 participants were included in the COVID-19 survey, including 2098 (63.1%) reported having NCDs at baseline and 1457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9 to 13.5%, and poor sleepers from 23.9 to 15.3%, while low physical activity increased from 13.4 to 25.2%, among participants with NCDs (P < 0.05 for all comparisons using McNemar's test). Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI 1.15-2.02). Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown.
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COVID-19 , COVID-19/epidemiologia , Doença Crônica , Controle de Doenças Transmissíveis , Depressão/epidemiologia , Humanos , Estilo de Vida , Estudos ProspectivosRESUMO
There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determine if men of African descent harbor a unique systemic immune-oncological signature and measure 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis are elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associates with metastatic and lethal prostate cancer, pointing to clinical importance. Moreover, two markers, pleiotrophin and TNFRSF9, predict poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.
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Neoplasias da Próstata , Proteômica , Negro ou Afro-Americano , População Negra/genética , Gana , Humanos , Masculino , Neoplasias da Próstata/patologiaRESUMO
Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.
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Asiático , Havaiano Nativo ou Outro Ilhéu do Pacífico , Havaí , Promoção da Saúde , Humanos , National Institutes of Health (U.S.) , Estados Unidos/epidemiologiaRESUMO
STUDY OBJECTIVES: To investigate the association between daytime napping and retinal microcirculation. METHODS: This is a cross-sectional study from a prospective population-based cohort. 2,662 participants were recruited after quota sampling. Information on napping was collected through face-to-face interviews. Retinal vascular calibers (RVCs), including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arterio-to-venous ratio (AVR), were obtained from fundus photography. Multivariate regression and restricted cubic spline curve were performed to determine the association between RVCs and daytime napping duration. RESULTS: 56.4% participants reported daytime napping regularly. Compared to no nap, daytime nap was related to higher CRAE, with nap duration of 0.5-1 h showing the most significant association. 0.5-1 h daytime nappers displayed an average of 4.18 µm (95% confidence interval [CI] 2.45-5.91, p < 0.001) wider CRAE than non-nappers after adjustment. No significant association was found between CRVE and daytime napping. Moreover, individuals with 0.5-1 h daytime napping had a lower risk for AVR reduction (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.56-0.86, p = 0.001) than non-nappers. Similar association persisted in non-hypertensive population. Restricted cubic spline indicated a J-shaped relationship between AVR reduction and nap duration. CONCLUSION: Retinal microcirculation was positively associated with self-reported 0.5-1 h daytime napping. Better indicators of retinal microcirculation were probably related to nap duration in a J-shaped manner. Also, the possibly beneficial role of 0.5-1 h daytime napping on retinal microcirculation might be independent of clinically diagnosed vascular diseases.
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Sono , China/epidemiologia , Estudos Transversais , Humanos , Microcirculação , Estudos ProspectivosRESUMO
PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multi-center, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI ≥ 30 kg/m2), 26% and 90% had WC > 97 cm and WHR > 0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive PCa, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR = 1.38, 95% CI 0.99-1.93), and central obesity (WC > 97 cm: OR = 1.60, 95% CI 1.10-2.33; and WHtR > 0.59: OR = 1.68, 95% CI 1.24-2.29) were positively associated with D'Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.
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Obesidade Abdominal , Neoplasias da Próstata , Índice de Massa Corporal , Estudos de Casos e Controles , Humanos , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Fatores de Risco , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
OBJECTIVE: Physical activity (PA) during COVID-19 shelter-in-place (SIP) may offset stress. This study examined associations between PA, stress and stress management strategies during SIP. DESIGN AND MAIN OUTCOME MEASURES: Participants (N = 990) from a cohort of Northern California adults completed surveys during early SIP (3/23/20-4/2/20) and mid-SIP (4/24/20-5/8/20). Participants self-reported past-month PA (meeting vs. not meeting guidelines), changes in stress (decreased/unchanged vs. increased) and use (yes/no) of 10 stress management strategies. We tested differences in mid-SIP stress and stress management strategies by PA, and differences in mid-SIP stress by stress management strategies. RESULTS: Compared to participants inactive at mid-SIP, active participants reported less stress (AOR = 0.60 [0.45, 0.81]). Active participants were more likely to manage stress using outdoor PA, indoor PA, yoga/meditation/prayer, gardening, and reading (AORs > 1.42), and less likely to sleep (AOR = 0.65 [0.48, 0.89]) or eat ([AOR = 0.48 [0.35, 0.66]) more. Managing stress using outdoor PA, indoor PA or reading was associated with lower stress; managing stress using TV/movies, sleeping or eating was associated with increased stress (ps < 0.05). CONCLUSIONS: Meeting PA guidelines during SIP was associated with less stress. Inactive participants reported greater sleeping and eating to cope; active participants used active stress management strategies. Engagement in physically active stress management was associated with lower stress.
Assuntos
COVID-19 , Exercício Físico , Humanos , Estudos Longitudinais , SARS-CoV-2 , Comportamento SedentárioRESUMO
Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population. Methods: We included 250 participants aged 20-80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex. Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status. Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).
RESUMO
Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus-North; Salvador-Northeast; Rondonópolis-Midwest and Rio de Janeiro-Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 -recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima's D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.
Assuntos
Malária/genética , Polimorfismo de Nucleotídeo Único , Piruvato Quinase/genética , Adulto , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Moçambique , Piruvato Quinase/deficiência , Adulto JovemRESUMO
OBJECTIVES: To determine the association of general practitioner (GP) contact with depressive symptoms during the COVID-19 pandemic and lockdown in China. DESIGN: In April 2020, a follow-up survey was conducted on the basis of a baseline survey conducted between October 2018 and May 2019. SETTING: The survey was embedded in the Stanford Wellness Living Laboratory-China (WELL China) study, an ongoing prospective community-based cohort study during 2018-2019. PARTICIPANTS: The survey was conducted by telephone interview among 4144 adult urban residents participating in the WELL China study at baseline. We collected information on sociodemographic characteristics, depressive symptoms and GP contact during the lockdown period (February to March 2020). PRIMARY AND SECONDARY OUTCOME MEASURES: Depressive symptoms were measured using the WHO-Five Well-being Index, comprising five questionnaire items that briefly indicate psychological well-being. Logistic regression models were applied to assess the association between GP contact and depressive symptoms. RESULTS: In total, 3356 participants responded to the survey; 203 were excluded owing to missing data on depressive symptoms, leaving 3153 participants in the present study. During lockdown, 449 participants had GP contact. GP contact was significantly negatively associated with prevalent depressive symptoms (OR, 0.67; 95% CI 0.51 to 0.89; p<0.01) and incident depressive symptoms (OR 0.68; 95% CI 0.51 to 0.93; p<0.05). Stratified analysis showed a significant negative association between depressive symptoms and GP contact in individuals who were 45-64 years old (p<0.01), had a middle or high education (p<0.01) and had self-reported non-communicable diseases (p<0.05). CONCLUSIONS: Contact with GPs during the COVID-19 pandemic and lockdowns may have a negative association with depressive symptoms in community-dwelling populations. Given the possibility of further surges in COVID-19 infections, GPs' contact in the community should be enhanced.